Systems and methods for optimization of plasma collection volumes

ABSTRACT

A plasmapheresis system and a method for operating a plasmapheresis system are provided by which the volume/weight of anticoagulated plasma that is collected is optimized. In one example, a nomogram is provided that utilizes the donor&#39;s hematocrit to calculate the volume/weight of raw plasma within a plasma product having the maximum volume permitted by the FDA nomogram. In a plasmapheresis procedure having multiple collection phases followed by a reinfusion cycle in which concentrated red blood cells are returned to the donor, the volume of plasma product to be collected is calculated prior to the start of each collection cycle to account for the donor&#39;s increasing hematocrit, thus resulting in a greater total volume of plasma product to be collected during the plasmapheresis procedure.

BACKGROUND

The present application relates to systems and method for performingplasmapheresis and, more particularly, to plasmapheresis systems andmethods in which the volume of source or raw plasma product that may becollected from a particular donor is optimized.

Plasmapheresis is an apheresis procedure in which whole blood iswithdrawn from a donor, the plasma separated from the cellular bloodcomponents (red blood cells, platelets and leukocytes) and retained, andthe cellular blood components returned to the donor. The separation ofthe plasma from the cellular components is typically accomplished in anautomated procedure by centrifugation or membrane filtration.

In automated plasmapheresis, whole blood is drawn from the donor, mixedat a specified ratio with anticoagulant (“AC”), and then separated intoanticoagulated plasma and red blood cells and other cellular components.Once a target volume of anticoagulated plasma (or “plasma product”) hasbeen collected, as determined by a weigh scale associated with a plasmacollection container, the withdrawal of whole blood from the donorceases, and the red blood cells and other cellular components arereturned to the donor. Often, the plasma product is collected inmultiple collection and reinfusion cycles, until the total target volumeof anticoagulated plasma has been collected. The anticoagulated plasmais used for later transfusion or further manufacturing.

Plasma that is collected to serve as a source material (“source plasma”)for further manufacturing is collected from multiple donors and combinedor pooled together for this purpose. The FDA issued guidelines forregistered blood collection centers as to the volume of plasma that maybe collected as source plasma during plasmapheresis in order to improvethe consistency of procedures for manufacturing source plasma, and tominimize the opportunity for staff error. (FDA Memo: “VolumeLimits-Automated Collection of Source Plasma (Nov. 4, 1992)”). The FDAMemo noted inconsistencies due to the various types of anticoagulantsolutions used, differing concentrations of the anticoagulant, and therange of anticoagulant to plasma ratios.

The FDA Memo set forth a simplified plasma volume nomogram, reproducedin the table shown in FIG. 1, in which the volume (or weight) of plasmathat may be collected from a particular donor is limited to ensure donorsafety and comfort. More specifically, the FDA nomogram limits thevolume (or weight) of plasma based on the weight of the donor, andestablishes the volume of anticoagulant that may be added to a 1:16ratio of anticoagulant to anticoagulated blood, or 0.06 partsanticoagulant to 1 part anticoagulated blood, to arrive at a maximumcollection volume for the total of the plasma plus the anticoagulant fora particular donor.

The simplified nomogram set forth in the FDA Memo has been thepredominant method for determining plasma product collection volumesused by blood collection centers. Therefore, the plasmapheresis devicesused at such centers are commonly programmed to collect a specifiedvolume/weight of anticoagulated plasma (assuming a known density) inaccordance with the maximum collection volume permitted by the FDAnomogram, with the anticoagulant being added to the whole blood at a1:16 or 0.06 ratio.

One simplification made in the FDA nomogram is to exclude theconsideration of donor hematocrit in determining the collection volumethe plasma product. However, the relative proportions of raw plasma andanticoagulant in the plasma product depends on the donor bloodhematocrit and the ratio at which the AC is combined with the donor'swhole blood. As a consequence, higher hematocrit donors reach themaximum collection volume set forth in the FDA nomogram before reachingthe maximum (raw) plasma volume that may be safely collected from thedonor. This represents an inefficiency for the plasma collection center,in that volume of raw plasma that is collected is less than the maximumamount possible.

Further, the amount of plasma that may be safely collected from a donorcan depend on factors in addition to the donor's weight and hematocrit,such as the donor's height, sex and age, as these factors affect thedonor's total blood volume (and volume of plasma).

Because the source plasma from multiple donors is combined, it isimportant to maximize the plasma volume that may be collected from eachindividual donor, as even small gains in volume collected from eachindividual donor, when added together, result in a meaningful increasein the total volume of the pooled plasma. If a plasmapheresis devicewere to be able to better target the raw plasma volume, more plasmaproteins could be collected from each donor, improving the overallefficiency of the plasma collection center. Accordingly, by way of thepresent disclosure, systems and methods for optimizing the volume ofplasma collected are provided which are consistent with donor safety andcomfort.

SUMMARY

By way of the present disclosure, methods are provided for operating aplasmapheresis system to collect a volume of anticoagulated plasmavolume (i.e., the plasma product) that insures that the total volume ofraw plasma in the plasma product is the maximum that may be collectedfrom a particular donor consistent with donor safety and comfort,whether as dictated the donor's unique physical characteristics, asindicated by the FDA nomogram or by some other methodology.

In keeping with a first aspect of the disclosure, a method is providedfor operating a plasmapheresis system to collect a plasma product volumethat comprises the maximum allowable volume/weight of raw plasma inaccordance with the limits set forth in the FDA nomogram based on theweight of the donor.

In order to collect the maximum volume/weight of raw plasma permitted bythe FDA nomogram, a modified nomogram is provided that utilizes thedonor's hematocrit to calculate a target volume/weight for a plasmaproduct having the maximum volume of raw plasma permitted by the FDAnomogram. A calculated volume/weight of raw plasma is compared to themaximum volume/weight for the raw plasma permitted by the FDA nomogram.If the calculated volume/weight of raw plasma is less than the maximumpermitted volume/weight, the volume/weight of the plasma product to becollected is adjusted upward from the maximum volume/weight permitted bythe FDA nomogram for the plasma product by an amount equal to thedifference plus the additional amount of anticoagulant that is added toprocess the additional volume/weight of plasma.

Thus, with the knowledge of the donor's hematocrit and the instrument'sAC ratio, the volume of additional raw plasma that may be safelycollected from the donor consistent with the limits set forth in the FDAnomogram is determined, and then the total volume/weight of plasmaproduct to be collected based on the weight of the donor set forth inthe FDA nomogram is adjusted accordingly.

Typically, plasmapheresis procedures involve sequential cycles ofalternating phases, one in which whole blood is withdrawn from the donorand the plasma separated and collected, and the other in which theseparated red blood cells and any other non-RBC cellular components arereturned to the donor. The donor's hematocrit will change during thecourse of the plasmapheresis procedure, thus affecting the amount ofanticoagulant in the plasma product collected from one cycle to thenext.

Consequently, in the first aspect of the disclosure, before thecommencement of the subsequent extraction/separation phase, a newhematocrit value for the donor is determined, and the targetvolume/weight of plasma product for the procedure is recalculated beforethe commencement of each extraction/separation phase to ensure that themaximum amount of raw plasma permitted by the FDA nomogram is collected.

In keeping with a second aspect, a further method for collecting avolume of plasma during an apheresis procedure is provided. The steps ofthe method comprise: determining a total whole blood volume V_(b) forthe donor; determining a volume of raw plasma (V_(RP)) that may becollected from the donor based on V_(b); determining a target volume ofplasma product (V_(PP)) to be collected, wherein V_(PP) is equal to thevolume of raw plasma (V_(RP)) to be collected plus a volume ofanticoagulant (V_(AC)) that is added to the V_(RP) during the apheresisprocedure, such that V_(PP)=V_(RP)*K, whereK=(ACR*(1−Hct/100)+1)/(ACR*(1−Hct/100)), based on an anticoagulant ratio(ACR, defined as the ratio of donor blood volume to anticoagulant volumefor donor blood having no anticoagulant) established for the procedureand a Hct of the donor; withdrawing whole blood from the donor; addinganticoagulant to the whole blood in an amount consistent with the ACR;separating plasma product from the whole blood; and transferring theplasma product to a collection container until the volume of plasmaproduct in the collection container reaches V_(PP). Because theplasmapheresis procedure comprises multiple extraction/separation andreturn phases, the V_(PP) for the procedure is recalculated before eachextraction/separation phase is commenced, based on a value for thehematocrit of the donor determined prior to the start of each drawphase, and the target volume for the plasma product adjustedaccordingly. Alternatively, V_(RP) may be determined based on acalculated value for the donor's total plasma volume, based on V_(b) andthe donor's hematocrit.

In a third aspect, a method for determining a volume of plasma product(V_(PP)) that may be collected during an apheresis procedure isprovided, wherein V_(PP) is equal to a volume of raw plasma (V_(RP))that may be collected plus a volume of anticoagulant (V_(AC)) that isadded to the V_(RP) during the apheresis procedure. The steps of themethod comprise: determining a weight (W_(kg)) and sex (M or F) of thedonor, determining a hematocrit (Hct) for the donor; determining thevolume of raw plasma (V_(RP)) that may be collected based on the weight(W_(kg)) and sex (M or F) of the donor; determining a ratio K betweenthe V_(PP) and the V_(RP), such that K=V_(PP)/V_(RP), based on ananticoagulant ratio (ACR) and the Hct of the donor; determining V_(PP),such that V_(PP)=V_(RP)*K. Further,K=(ACR*(1−Hct/100)+1)/(ACR*(1−Hct/100)). After V_(PP) is determined,whole blood is withdrawn from the donor; anticoagulant is added to thewhole blood in an amount consistent with the ACR; plasma product isseparated from the whole blood; and plasma product is transferred to acollection container. After a desired amount of whole blood has beenwithdrawn from the donor, the red blood cells are returned to the donor.Then, the Hct of the donor and V_(PP) are determined prior to each drawphase.

In a related aspect, the draw and separation steps are repeated untilthe volume of plasma product in the collection container reaches V_(PP).

In a related aspect, the donor's hematocrit subsequent to the firstcollection phase may be calculated by a volume balance, assuming thatthe donor's quantity of red blood cells is the same at the start of eachdraw cycle, while the total volume of blood decreases from one cycle tothe next in an amount equal to the amount of raw plasma collected.Alternatively, the donor's hematocrit at the start of each draw cyclecan be measured by an optical or other sensor.

In a further aspect, the volume of raw plasma that may be collected froma particular donor may be determined by any one of several differentmeans. Such means include, e.g., the FDA nomogram, taking into accountonly the donor's weight; a modified FDA nomogram, further taking intoaccount the donor's hematocrit, and taking a fraction of a total bloodvolume or total plasma volume calculated for a particular donor. Thetotal blood volume or total plasma volume may be determined using, forexample, Nadler's equations, Gilcher's Rule of Five, tables provided bythe International Council for Standardization in Haematology (ICSH), orany other generally accepted method using the donor's height, weight,sex and age, consistent with the safety and comfort of the donor.

In a fourth aspect, an automated system for separating plasma from wholeblood is provided that comprises a reusable hardware component and adisposable kit. The disposable kit further comprises i) a separator forseparating whole blood into a plasma fraction and a concentrated cellfraction, the separator having an input having a blood line integrallyconnected thereto for transporting whole blood from a donor to theseparator, a plasma output port integrally connected to a plasmacollection container by a plasma line, and a concentrated cell outletport integrally connected to a reservoir for receipt of concentratedcells prior to reinfusion to the donor; ii) a donor line terminating ina venipuncture needle for transporting whole blood from a donor to theblood line, iii) an anticoagulant line integrally connected to the bloodline and configured to be connected to a source of anticoagulant fortransporting anticoagulant to the donor line, and iv) a reinfusion linefor transporting concentrated cells from the reservoir to the donorline.

The reusable hardware component further comprises i) a first peristalticpump for delivering anticoagulant at a controlled rate into the bloodline during a collection phase, ii) a second pump for deliveringanticoagulated whole blood to the separator during the collection phaseand for returning concentrated cellular components during a reinfusionphase, iii) a third pump for delivering concentrated cellular componentsfrom the separator to the reservoir during the collection phase, iv) aclamp associated with each of the blood line, plasma line, andreinfusion line, v) a weigh scale for weighing each of the plasmacollection container, the reservoir and the source of anticoagulant, andvi) a programmable controller comprising a touch screen for receivinginput from an operator, the programmable controller configured toreceive a signal from each of the weigh scales and to automaticallyoperate the first, second and third pumps and the clamps to separatewhole blood into a plasma fraction and a concentrated cell fractionduring the collection phase and to return concentrated cells to thedonor during the reinfusion stage. The programmable controller isfurther configured to determine a target amount for the plasma productto be collected in the plasma collection container in accordance withany of the methods described herein, and to terminate the collectionphase upon receiving a signal that the amount of plasma product in theplasma collection container equal to the target amount of the plasmaproduct determined by the controller. In determining the target amountfor the plasma product to be collected, the controller may be configuredto calculate the hematocrit of the donor prior to the collection phaseof each cycle. Alternatively, or additionally, the controller mayreceive a signal from a sensor or the like that is indicative of thedonor's hematocrit. Further, the amount of plasma product in the plasmacollection container may be determined by, e.g., the weigh scaleassociated with the plasma collection container or an optical sensorthat directly measures the volume.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a table showing the simplified nomogram presented in the FDAMemo: “Volume Limits-Automated Collection of Source Plasma (Nov. 4,1992)”.

FIG. 2 is a perspective view of an exemplary plasmapheresis instrumentsuitable for use in the system and method of the present application.

FIG. 3 is a perspective view of a spinning membrane separator of thetype incorporated in a disposable set, with portions broken away to showdetail, usable with the plasmapheresis system of FIG. 2.

FIG. 4 is a perspective view of the front panel of the plasmapheresissystem of FIG. 2 showing the components of the disposable set that aremounted thereto.

FIG. 5 is a schematic view showing operation of the plasmapheresissystem in the collection phase.

FIG. 6 is a schematic view showing operation of the plasmapheresissystem in the reinfusion phase.

FIG. 7 is a table that shows the volume of raw plasma, based on donorhematocrit, that is contained within a plasma product volume limit setby the FDA nomogram using a 1:16 ratio of anticoagulant to whole blood.

FIG. 8 is a table that shows the volume of “unclaimed” raw plasma in theplasma product based the difference between the values set forth in FIG.7 and the maximum volume of raw plasma that may be collected based onthe FDA nomogram.

FIG. 9 is a table that shows the volume of plasma product that may becollected from a donor, based on the donor's weight and hematocrit, thatresults in the maximum permissible volume of raw plasma permitted by theFDA nomogram.

FIG. 10 is a table showing the inputs to a programmable controller forperforming a hypothetical plasmapheresis procedure in accordance withthe method of the present application.

FIGS. 11a, 11b comprise a table, broken into two parts illustrating howthe donor's hematocrit increases over the course of a hypotheticalplasmapheresis procedure based on the inputs from the table of FIG. 10,and resulting in an increase in the total collection volume of plasmaproduct necessary to collect the target volume of raw plasma.

FIG. 12 is a graph illustrating IgG dilution during plasmapheresis.

DETAILED DESCRIPTION

A more detailed description of the systems and methods in accordancewith the present disclosure is set forth below. It should be understoodthat the description below of specific devices and methods is intendedto be exemplary, and not exhaustive of all possible variations orapplications. Thus, the scope of the disclosure is not intended to belimiting, and should be understood to encompass variations orembodiments that would occur to persons of ordinary skill.

In the context of the present application, plasmapheresis is performedon an automated system comprising a hardware component, generallydesignated 10, and a disposable set, generally designated 12, to collectplasma to be processed as source plasma. With reference to FIGS. 2-6,and as described in greater detail below, the disposable set 12 consistsof an integrally connected separator, containers, and tubing totransport blood and solutions within a sterile fluid pathway.

The separator 14, best seen in FIG. 3, has a spinning membrane filter 16mounted to a rotor 18 for rotation within a case 20 to separate bloodinto components. A detailed description of a spinning membrane separatormay be found in U.S. Pat. No. 5,194,145 to Schoendorfer, which isincorporated herein by reference. As can be appreciated, in a differentsystem, separation of the whole blood may be accomplished bycentrifugation. See, e.g. U.S. Pat. No. 5,360,542 to Williamson et al.

During plasmapheresis, anticoagulated whole blood enters the separator14 through a whole blood input port 22. The plasma is separated by thespinning membrane filter and then passes out of a plasma output port 24,through a plasma line 26, and into a plasma collection container 28.Concentrated cells are pumped out of a concentrated cell output port 30into a reservoir 32, where the cells remain until reinfusion to thedonor.

The disposable set 12 also includes tubing lines for introducing wholeblood from the donor into the system during collection and returningconcentrated cells to the donor during reinfusion (donor line 34, whichterminates in the venipuncture needle 36), and for transportinganticoagulated whole blood to the separator (blood line 38),concentrated cells into the reservoir (cell line 40), concentrated cellsfrom the reservoir to the donor line (reinfusion line 42), plasma intothe plasma collection container (plasma line 44), saline (saline line46), and anticoagulant (AC line 48).

The hardware component 10 includes a programmable controller 50 andtouch screen 52 with a graphical user interface (“GUI”) through whichthe operator controls the procedure. For example, the GUI permits entryof any of a donor ID, donor sex, donor height, donor weight, donor age,donor hematocrit/hemoglobin; a target saline infusion volume (if asaline protocol is selected), and a target plasma volume. The touchscreen 52 also enables the operator to gather status information andhandle error conditions.

Three peristaltic pumps are located on the front panel of the hardwarecomponent 10, including an AC pump 54, a blood pump 56, and a cell pump58. The AC pump 54 delivers anticoagulant solution (AC) at a controlledrate into the blood line 38 as whole blood enters the set from thedonor. The blood pump 56 delivers anticoagulated whole blood to theseparator during the collection phase of the procedure and returnsconcentrated cellular components and, if desired, replacement fluid tothe donor during the reinfusion phase of the procedure. The cell pump 58delivers concentrated cellular components from the separator 14 to areservoir during the collection phase.

The front panel also includes four clamps into which the disposable set12 is installed, including a reinfusion clamp 60, a blood clamp 62, asaline clamp 64, and a plasma clamp 66. The reinfusion clamp 60 closesto block the reinfusion line (42) during the collection phase (FIG. 5)and is open during the reinfusion phase (FIG. 6) to allow the blood pumpto reinfuse the concentrated cellular components from the reservoir 32to the donor. The blood clamp 62 opens during the collection phase toallow anticoagulated whole blood to be pumped to the separator 14 andcloses during the reinfusion phase to block the blood line 38. Thesaline clamp 64 closes to block the saline line 46 during the collectionphase and during reinfusion of the separated cellular components. Ifsaline is to be used as a replacement fluid, the saline clamp 64 opensduring the reinfusion phase. The plasma clamp 66 opens during thecollection phase to allow plasma to flow into the plasma collectioncontainer 28 and closes during the reinfusion phase.

The hardware component 10 includes three weigh scales to monitor thecurrent plasma collection volume (scale 68), the AC solution volume(scale 70), and the concentrated cellular content volume (scale 72). Thesystem also includes various sensors and detectors, including a venouspressure sensor 74, a separator pressure sensor 76, optical blooddetectors 78, and an air detector 80.

The donor is connected to the system throughout the procedure. Asillustrated, the disposable set 12 includes a single venipuncture needle36, through which whole blood is drawn from the donor in a collectionphase (FIG. 5) and concentrated cells are returned to the donor in areinfusion stage (FIG. 6). As noted above, the plasmapheresis proceduremay comprise a plurality of cycles each having a collection/separationphase followed by a return or reinfusion phase. During the collectionphase, the whole blood is separated into plasma and concentrated cells.The disposable set includes a plasma collection container 28 for receiptof the separated plasma and a reservoir 32 for receipt of theconcentrated cells. During the reinfusion phase, the concentrated cellsfrom the reservoir 32 are reinfused to the donor through thevenipuncture needle 36. Typically, plasmapheresis performed with asingle venipuncture needle 36 involves multiple cycles of collection andreinfusion.

Returning to FIG. 5, during the collection phase, anticoagulant solution(AC) is pumped at a controlled rate and mixed with whole blood as itenters the disposable set 12. The anticoagulated blood is pumped to theseparator 14, where plasma is separated from the cellular components anddirected to the plasma collection container 28.

The cellular components are pumped from the separator 14 to thereservoir 32. The collection phase stops when the reservoir 32 reachesan expected volume of concentrated cells or if the target plasmacollection volume has been achieved.

Then, the reinfusion phase begins. With reference to FIG. 6, during thereinfusion phase, the blood pump 56 reverses direction and pumps theconcentrated cells from the reservoir 32 back to the donor through theapheresis needle 36. If a saline protocol was selected, by which salineis returned to the donor as a replacement fluid for the collectedplasma, the final reinfusion phase is followed by saline infusion.

In keeping with one aspect of the disclosure, the automated plasmacollection device is configured to collect a volume/weight ofanticoagulated plasma (i.e., the plasma product) having the maximumvolume/weight of raw plasma permitted for the donor under the limits setforth in the FDA nomogram. In order to maximize the volume of raw plasmacomprising the plasma product, the device is programmed with a nomogramthat accounts for the donor's hematocrit. With the knowledge of thedonor's hematocrit and the instrument's AC ratio, the totalvolume/weight of plasma product to be collected can be determined suchthat the plasma product includes the maximum volume/weight of raw plasmafraction that may be collected from a donor, consistent with the limitsfor total volume/weight of raw plasma set forth in the FDA nomogram. Byhaving the computations programmed into the controller, the likelihoodof operator error is diminished in comparison to the off-linecalculation of the collection volume that is then entered into theinstrument.

During plasmapheresis, when anticoagulant is mixed with whole blood asit is drawn from the donor, the anticoagulant is evenly distributedwithin the raw plasma in the blood. However, the amount of raw plasma inthe whole blood is dependent on the hematocrit (Hct) of the whole blood.The following relationships are established:

Volume of RBC=Volume of Whole Blood*Hct/100.  [1]

Volume of Raw Plasma=Volume of Whole Blood*(1−Hct/100).  [2]

When anticoagulant is mixed with the whole blood, it is typicallymetered at an AC Ratio (ACR) of 16 parts of whole blood to 1 part of AC,or at 1 part of whole blood to 0.06 parts of AC.

ACR=Volume of Whole Blood/Volume of Anticoagulant(the donor blood havingno anticoagulant).  [3]

(This yields a slightly different result from the FDA nomogram, which,as noted above, standardizes the volume of anticoagulant that may beadded to a 1:16 ratio of anticoagulant to anticoagulated blood, or 0.06parts anticoagulant to 1 part anticoagulated blood.)

Volume of Anticoagulated Blood=Volume of Anticoagulant+Volume of WholeBlood.  [4]

Combining equations gives:

Volume of Raw Plasma=ACR*Volume of Anticoagulant*(1−Hct/100).  [5]

Since the red cells are given back to the donor:

Volume collected Plasma=Volume of Raw Plasma+Volume ofAnticoagulant.  [6]

Equations [5] and [6] can be combined to calculate the amount ofanticoagulant in a given amount of collected plasma:

Volume of Anticoagulant=Volume of collectedplasma/(1+ACR*(1−Hct/100)).  [7]

Further:

Volume of collected Plasma=Volume of Raw Plasma*K, whereK=(ACR*(1−Hct/100)+1)/(ACR*(1−Hct/100)).  [8]

In view of the relationships expressed in the equations above, thevolume of raw plasma contained within the volume of plasma productpermitted under the FDA nomogram can be determined based upon thehematocrit of the donor. The results of such calculations are set forthin FIG. 7, which shows the volume of raw plasma based on donorhematocrit that is contained within a plasma product volume limit set bythe FDA nomogram.

As can be appreciated with reference to FIG. 7, for donors weighing from110 to 149 lbs. (for whom the maximum plasma product volume per the FDAnomogram is 690 mL), if the donor has a hematocrit of 42 or greater, thevolume of raw plasma collected is less than the 625 mL permitted by theFDA nomogram. The situation is similar for donors having a weight of 150to 174 lbs. (for whom the maximum plasma collection volume per the FDAnomogram is 825 mL) and for donors having a weight of 175 lbs. and up(for whom the maximum plasma collection volume per the FDA nomogram is880 mL) when the donor's hematocrit is 40 or greater.

The table set forth in FIG. 8 presents the volume of “unclaimed” rawplasma in the plasma product based the difference between the values setforth in FIG. 7 and the maximum volume of raw plasma that may becollected based on the FDA nomogram. Thus, as shown in the table setforth in FIG. 9, the plasma product collected from any particular donormay be adjusted from that set forth in the FDA nomogram by an amountcorresponding to the amount of “unclaimed” raw plasma set forth in FIG.8 plus the amount of anticoagulant needed to process the additionalvolume.

Alternatively, the volume of plasma product to be collected may becalculated by first determining a weight and hematocrit (Hct) for thedonor; determining the volume of raw plasma (V_(RP)) that may becollected based on the weight of the donor (W_(kg)); determining a ratioK between the V_(PP) and the V_(RP), such that K=V_(PP)/V_(RP), based onan anticoagulant ratio (ACR; 1:16 or 0.06:1, per the FDA nomogram) andthe Hct of the donor; and determining V_(PP), such that V_(PP)=V_(RP)*K.Further, K=(ACR*(1−Hct/100)+1)/(ACR*(1−Hct/100)).

In a further alternative, the volume of plasma product that is to becollected (V_(PP)) may be calculated by first determining the weight(W_(kg)) and hematocrit (Hct) of the donor; determining the volume ofraw plasma (V_(RP)) that may be collected based on the weight of thedonor (W_(kg)); determining the volume of anticoagulant to be added(V_(AC)) based on the anticoagulant ratio (ACR; 1:16 or 0.06:1, per theFDA nomogram) and the hematocrit of the donor such thatV_(AC)=V_(RP)*(ACR*(1−Hct/100)); and determining the collection volumesuch that V_(PP)=V_(RP)+V_(AC).

Various methods may be used for determining the volume of raw plasmathat may be collected based on the weight of the donor. For example, theweight of the donor may be multiplied by an established constant “K₁”(such as 10 mL/kg). Alternatively, the weight of the donor may besegregated into weight categories, with a fixed volume established foreach category (as in the FDA nomogram discussed above, in which theranges of donor weight are divided into three categories).

Alternatively, a donor's plasma volume may be estimated based on thedonor's total blood volume, and a volume of plasma that may be harvestedconsistent with donor safety and comfort may be based on thisestimation. Methods utilizing donor parameters are commonly usedestimate a donor's total blood volume. Examples of such methods includeNadler's equations (that take into account the height, sex and weight ofthe donor), Gilcher's Rule of Five (that takes into account sex, weightand morphology (obese, thin, normal or muscular), or the standards ofthe International Counsel for Standardization in Haematology (“ICSH) asset forth in Br. J. Haem. 1995, 89:748-56) (that take into account theheight, weight, age and sex of the donor). Any other generally acceptedmethodology for determining donor's total blood volume may also be used.Once the donor's total blood volume is determined, the donor's plasmavolume may be estimated by multiplying the total blood volume by aconstant “K₂”, where or K₂ equals (1−Hct of the donor).

From an analysis of demographic, examination, and laboratory data fromthe 2015-2016 National Health and Nutrition Examination Survey, in whichsex, age, height, weight, pregnancy data and hematocrit were extracted,presented in Pearson et al., Interpretation of measured red cell massand plasma volume in adults: Expert Panel on Radionuclides of theInternational Council for Standardization in Haematology, British J.Haematology, 89: 748-756 (1995), (upon which the ICSH recommendedformulae were derived), it has been determined that for donors havingcertain characteristics (namely low weight females with highhematocrits), up to 36% of the available plasma may be collected whilestaying within current regulations. Plasmapheresis procedures with suchdonors have been carried out routinely without adverse reactions, andthus are considered safe. This suggests that up to 36% of a donor'savailable plasma can be safely collected in a plasmapheresis procedure.

Given that only negative deviations of a donor's true blood volume froma predicted/calculated total blood volume present a potential risk, afurther adjustment downward of the harvestable volume of plasma may beappropriate. Based on a consideration of the deviation between thecalculated blood volume as determined in Pearson et al., cited above,and the experimental blood volume data presented in Retzlaff et al.,Erythrocyte Volume, Plasma Volume, and Lean Body Mass in Adult Men andWomen, J. Haematology, 33, 5:649-667 (1969), there is a 95% confidencethat an individual's predicted blood volume will differ not more that20.5%. Thus a scaling factor of 0.795 may be applied to determination ofharvestable raw plasma being 36% of the donor's total plasma volumedescribed above, so that 28.6% of a donor's calculated volume of rawplasma may be harvested, consistent with donor safety and comfort.

Alternatively, an adjustment V_(C) may be made to the calculated volumeof whole blood V_(WB) before calculating the volume of harvestableplasma V_(RP), such the V_(RP)=0.36(1−Hct)(V_(WB)− V_(C)). A regressionanalysis of the data presented by Retzlaff resulted in a determinationof V_(C)=523 mL.

Thus, the collection volume (the volume of plasma product) is determinedbased on the volume of raw plasma volume that may be collected from aparticular donor, the donor's hematocrit, and the fixed anticoagulantratio (ACR). Consequently, this methodology allows for more consistentcontrol for the raw plasma volume of the donor, which is the variablemost related to donor safety.

In practice, the operator enters into the system controller thecollection volume for the plasma product for the particular donor, basedon the target volume of raw plasma that may be harvested. The targetplasma collection volume may be as set forth in FIG. 9, based on thedonor's weight and hematocrit for the initial collection phase, or byany of the other methods as set forth above. Alternatively, thecontroller is configured to calculate the target plasma productcollection volume for the initial collection phase in accordance with amethodology such as those described above upon the operator entering,e.g., the donor's weight and hematocrit, and/or any of the additionaldonor-specific information (such as the donor's sex, height and age)required by the methodologies used for determining a donor's total bloodvolume, total plasma volume, and the target volume of harvestable plasmathat may be collected. In a further alternative, the plasma collectiondevice may be integrated with a donor management system, by which donorparameters used for qualification screening (such as weight, hematocrit,etc.) can be electronically sent to the instrument, eliminating theopportunity for operator error in entering the donor parameters. Thedonor management system could also utilize the donor screeningmeasurements, along with the relationship between raw plasma volume andcollection volume, to automatically calculate a plasma collection volumethat it would transmit to the controller of the plasmapheresis device.

As noted above, plasmapheresis procedures are performed with multiplecycles of collection/draw phases and return/reinfusion phases. If thereturn/reinfusion phase does not include reinfusion of a replacementfluid, the donor's hematocrit will increase from one cycle to the next.Consequently, if the target volume for plasma product is determinedbased only on the donor's initial hematocrit, and does not take intoaccount the donor's increasing hematocrit, the volume of anticoagulantin the plasma product will be greater (and the volume of raw plasmaless) than what was predicted by the initial calculation for determiningthe target volume of plasma product. Thus, in order to ensure that thevolume of plasma product that is collected contains the maximum volumeof raw plasma that was determined to be harvested from a particulardonor, the target volume for plasma product is recalculated periodicallythroughout the plasmapheresis procedure, such as before the start of thecollection phase of each cycle, to take into account the change in thedonor's hematocrit.

Accordingly, a determination of the target volume for plasma productbased on the donor's starting hematocrit is made. The plasmapheresisprocedure commences with a first draw phase until a specified volume ofwhole blood (typically approximately 500 mL) has been withdrawn from thedonor. Anticoagulant is added to the whole blood and the anticoagulatedwhole blood is separated into a plasma product, red blood cells, andother non-RBC blood components. At the conclusion of the first drawphase, the red blood cells and non-RBC blood components are returned tothe donor. The current volume of plasma product collected after thefirst draw phase is determined by, e.g., the weigh scale. Then a currentvalue for the hematocrit of the donor is established and a new targetvolume of plasma product to be collected is determined, and the secondcycle of draw and return phases is performed. The cycle of draw andreturn phases is repeated until the target volume of plasma product torthe plasmapheresis procedure is collected, as recalculated prior to thestart of each draw phase. After the final collection phase, thecontroller initiates the final red blood cell reinfusion stage, afterwhich the donor is disconnected.

The benefits of performing a plasmapheresis procedure having multiplecollection/reinfusion cycles in accordance with the methodology setforth above may be seen by reference to the tables of FIGS. 10 and 11 a,11 b. FIG. 10 displays the input data for a hypothetical plasmapheresisprocedure for a donor weighing 190 lbs. (86.4 kg) and having an initialhematocrit of 44. With reference to the table of FIG. 1, the simplifiedFDA nomogram would limit the volume of plasma to be collected from sucha donor to 800 mL, and the total collection volume for the plasmaproduct to 880 mL. In the present example, the FDA nomogram limit on thevolume of raw plasma that may be collected is for illustrative purposesonly. As set forth above, other methodologies may be used to determinethe amount of raw plasma that may be safely extracted from a donor thatwould differ from that indicated by the FDA nomogram.

The number of collection and reinfusion cycles in a plasmapheresisprocedure may vary from three to twelve. In the hypotheticalplasmapheresis procedure, there are five collection and reinfusioncycles, which are chosen for illustrative purposes.

Before the commencement of the first collection cycle, the volume of rawplasma to be collected and the total target volume of plasma product tobe collected are determined in accordance with the methodologiesdescribed above, based on the donor's initial hematocrit. As set forthin the first row of the table (Cycle 1 start), the initial target volumefor the plasma product to be collected is 889 mL, which is the same asindicated by the table of FIG. 9 for a donor having a weight of 175 lbs.and up and a hematocrit of 44 in order to harvest the FDA limit of 800mL of raw plasma from the donor.

During each collection phase, 500 mL of whole blood is drawn from thedonor, to which anticoagulant is added at a predetermined ratio (i.e.,1:16), such that 31 mL is added for each collection cycle of 500 mL. Thewhole blood plus anticoagulant is separated into a plasma fraction and ared blood cell fraction.

During the first return phase (Cycle 1 return end), the red blood cellsand “non-RBC” blood components are returned to the donor, so that at theend of the first return cycle the donor's hematocrit has increased to45.6%, as calculated by the controller based on a blood volume beingdecreased by the amount of raw plasma collected, while the quantity ofred blood cells in the total blood volume remains the same as at thestart of the procedure. The controller can also account for the volumeof anticoagulant that is reinfused in each return phase along with thered blood cells, as well as the residual anticoagulant in the donor'swhole blood being drawn in cycles 2 and following, when determining thenew hematocrit value for the next cycle. The volume of raw plasma andthe total target volume of plasma product to be collected for theprocedure are then recalculated based on the donor's new, increasedhematocrit and raw plasma volume. This provides for a new total targetcollection volume of 891 mL.

The second collection phase is then performed, resulting in a total of430 mL of plasma product comprising 386 mL of raw plasma being collectedover the first two collection phases (Cycle 2 draw end). The red bloodcells and “non-RBC” blood components are again returned to the donor,after which the donor's hematocrit is calculated to be 47.2%.

Two more collection phases of 500 mL are performed, each followed by areturn phase, in which new values for the volume of raw plasma and totalvolume of plasma product to be collected are determined before the startof each collection phase. With the increasing hematocrit of the donor,the recalculated target collection volume for procedure increases to 893mL (for the third collection phase) and then to 894 mL (for the fourthcollection phase). A fifth “mini” collection cycle is performed to bringthe volume of raw plasma collected up to the 800 mL permitted by the FDAnomogram for the hypothetical donor. The recalculated target collectionvolume of plasma product for the fifth collection phase remains at 894mL.

Thus, as illustrated in the example above, when the target collectionvolume for the plasma product is recalculated for each collection phase,a target collection volume for the plasma product of 894 mL is obtained,which is required in order to collect the target volume of raw plasma of800 mL. In contrast, 889 mL of plasma product would have been collectedif the target collection volume is determined based only on the donor'sinitial hematocrit, or 880 mL if the target collection volume is basedon the simplified FDA nomogram. In both cases, less than the targetvolume of 800 mL would have been collected.

As can be appreciated, the greater the accuracy with which thehematocrit of the donor can be determined, both before and during theprocedure, the more likely the target volume of plasma product collectedwill include the maximum volume of raw plasma that can be collected fora particular donor. As described above, the hematocrit of the donorduring the procedure is based on the assumptions that 100% of the redblood cells that are withdrawn in each draw cycle are reinfused in eachreturn cycle, along with 100% of the non-RBC cellular products and avolume of anticoagulant. However, it has been determined that during thecourse of a blood separation procedure, interstitial fluid can shift tothe intravascular space, resulting in restoring half of the withdrawnvolume. See, Saito et al., Interstitial fluid shifts to plasmacompartment during blood donation, Transfusion 2013; 53(11):2744-50. Theshifted interstitial fluid is in addition to the red blood cells,non-RBC cellular products, and anticoagulant that are reinfused in eachreturn phase. Thus, accounting for the shift of interstitial fluid wouldresult in a more accurate hematocrit determination, and thus a moreaccurate determination of the target volume for plasma product that willresult in the maximum amount of raw plasma.

The shift of interstitial fluid during plasmapheresis has beensubstantiated by tracking the level of Immunoglobulin G (IgG) of a donorover the course of a plasmapheresis procedure. See, e.g., Burkhardt etal., Immunoglobulin G levels during collection of large volume plasmafor fractionation; Transfusion 2017; 56:417-420. If no interstitialfluid was being shifted, the IgG level of the donor would be stable overthe course of the plasmapheresis procedure. However, the IgG level hasbeen shown to drop, and the amount that the IgG level drops is afunction of the volume of interstitial fluid that has shifted to theblood system.

With reference to FIG. 12, a plot of volume of plasma collected (alongthe X-axis versus IgG concentration (along the Y-axis) that wasdeveloped empirically is shown. A 9% drop of the donor's IgG is seenfrom the baseline of zero plasma collected (at the start of theprocedure) to 200 mL of plasma collected, and a drop of an additional 4%from 200 mL to 800 mL collected. This was attributable to a shift ofinterstitial fluid equal to approximately 9% of the donor's initialtotal blood volume (after 200 mL of plasma being collected) toapproximately 13% of the donor's initial total blood volume (after 800mL of plasma being collected).

Based on the plot of FIG. 12, the following relationship between theamount that the donor's IgG concentration and the volume of plasmacollected has been established: y=1.0017x^(−0.02), where y=IgGconcentration and x=plasma volume collected. Thus, the percentage of thedonor's blood volume that is replaced by the shift of interstitial fluidis equal to V_(b)(1−y), where V_(b) is the donor's initial volume ofwhole blood. Thus, the shifted volume of interstitial fluid can becalculated based on the volume of plasma collected, and this amount canbe added to the volume of red blood cells, non-RBC cellular products andanticoagulant reinfused in each return phase to determine the currenttotal blood volume, and thus hematocrit, of the donor. As can beappreciated, the controller can be configured to automatically determinethe volume of interstitial fluid that has shifted based on the volume ofplasma collected, and to include the shifted volume when determining thedonor's hematocrit prior to each draw phase.

Alternatively, other methods that directly measure the donor'shematocrit may be employed, such as an optical sensor or, if acentrifugal separator is being used, measuring the volume of red bloodcells in the centrifuge.

In addition, anticoagulant is commonly introduced into the disposablekit prior to the commencement of the plasmapheresis procedure inpre-processing steps, such as for priming the disposable kit, performingone or more pre-cycles, or for performing other pre-procedure steps. Tothe extent that anticoagulant used for these purposes is ultimatelydirected to the plasma product collection container, it may be accountedfor in determining the volume contained in the plasma collectioncontainer that results in the target volume of raw plasma beingcollected. This may be done, for example, by measuring the weight of the“full” container of anticoagulant and the weight of the container ofanticoagulant prior to the commencement of the first draw cycle, andadding that volume of anticoagulant to the target volume of plasmaproduct. The controller can be configured to automatically perform thesteps necessary to account for the anticoagulant introduced into theplasma collection container separately from the anticoagulated plasma.

The methods and system set forth above have several aspects. In a firstaspect, a method for collecting plasma in which plasma product iscollected in multiple collection phases between which separated redblood cells are reinfused to the donor is provided. The method of thisfirst aspect comprises a) determining a volume of whole blood (V_(b))and hematocrit (Hct) for a donor; b) determining a volume of raw plasma(V_(RP)) that may be collected from the donor; c) determining a volumeof plasma product (V_(PP)) that may be collected, wherein the plasmaproduct comprises the raw plasma volume plus a volume of anticoagulant;d) withdrawing whole blood from the donor; e) introducing anticoagulantinto the withdrawn whole blood at a specified ratio (ACR); f) separatingthe withdrawn whole blood into a plasma product and a second componentcomprising red blood cells; g) collecting the plasma product in a plasmacollection container; h) after a desired amount of whole blood has beenwithdrawn from the donor, returning the red blood cells to the donor;and i) determining the Hct of the donor and V_(PP) prior to eachcollection phase.

In a second aspect, steps d)-i) are continued until a measured volume ofplasma product in the collection container equals V_(PP).

In a third aspect, a method for collecting plasma in which plasmaproduct is collected in multiple collection phases between whichseparated red blood cells are reinfused to the donor is provided. Themethod of this second aspect comprises: a) determining a volume of wholeblood (V_(b)) and hematocrit (Hct) for a donor; b) determining a volumeof raw plasma (V_(RP)) that may be collected from the donor based onV_(b); c) determining a volume of anticoagulant V_(AC) to be added tothe V_(RP) based on an anticoagulant ratio (ACR) and the Hct of thedonor, such that V_(AC)=V_(RP)*(ACR*(1−Hct)); d) determining a volume ofplasma product (V_(PP)) that may be collected, wherein the plasmaproduct comprises the raw plasma volume (V_(RP)) plus the volume ofanticoagulant (V_(AC)); e) withdrawing whole blood from the donor; f)introducing anticoagulant into the withdrawn whole blood at thespecified ratio (ACR); g) separating the withdrawn whole blood into aplasma product and a second component comprising red blood cells; h)collecting the plasma product in a plasma collection container; i) aftera desired amount of whole blood has been withdrawn from the donor,returning the red blood cells to the donor; and j) determining the Hctof the donor and V_(PP) prior to each collection phase.

In a fourth aspect, steps d)-j) are continued until a measured volume ofplasma product in the collection container equals V_(PP).

In a fifth aspect, V_(b) is determined based on one or more donorspecific characteristics including a donor's weight, height, sex, age,and morphology.

In a fourth aspect, a method is provided for collecting a volume ofplasma product (V_(PP)) in an apheresis procedure in which plasmaproduct is collected in multiple collection phases between whichseparated red blood cells are reinfused to the donor. In the method ofthis fourth aspect, V_(PP) is equal to a volume of raw plasma (V_(RP))that may be collected from a donor plus a volume of anticoagulant(V_(AC)) that is added to the V_(RP) during the apheresis procedure. Thesteps of the method comprise: a) determining a weight (W_(kg)) and sex(M or F) for the donor; b) determining a hematocrit (Hct) for the donor;c) determining the volume of raw plasma (V_(RP)) that may be collectedbased on the weight (W_(kg)) and sex (M or F) of the donor; d)determining a ratio K between the V_(PP) and the V_(RP), such thatK=V_(PP)/V_(RP), based on an anticoagulant ratio and the Hct of thedonor; e) determining V_(PP), such that V_(PP)=V_(RP)*K; f) withdrawingwhole blood from the donor; g) introducing anticoagulant into thewithdrawn whole blood at a specified ratio (ACR); h) separating thewithdrawn whole blood into a plasma product and a second componentcomprising red blood cells; i) collecting the plasma product in a plasmacollection container; j) after a desired amount of whole blood has beenwithdrawn from the donor, returning the red blood cells to the donor;and k) determining the Hct of the donor and the target V_(PP) prior toeach collection phase.

In a fifth aspect, steps c)-k) are repeated until a measured volume ofplasma product in the collection container equals V_(PP). Preferably,K=V_(PP)/V_(RP)=(ACR*(1−Hct/100)+1)/(ACR*(1−HCT/100)).

In a fifth aspect, a method is provided for collecting a volume ofplasma product (V_(PP)) in an apheresis procedure in which plasmaproduct is collected in multiple collection phases between whichseparated red blood cells are reinfused to the donor. In this fifthaspect V_(PP) is equal to a volume of raw plasma (V_(RP)) that may becollected from a donor plus a volume of anticoagulant (V_(AC)) that isadded to the V_(RP) during the apheresis procedure. The steps of themethod comprise: a) determining a weight (W_(kg)) and sex (M or F) forthe donor; b) determining a hematocrit (Hct) for the donor; c)determining the volume of raw plasma (V_(RP)) that may be collectedbased on the weight of the donor (W_(kg)) and the sex (M or F) of thedonor; d) determining the V_(AC) to be added to the V_(RP) based on ananticoagulant ratio (ACR) and the Hct of the donor, such thatV_(AC)=V_(RP)*(ACR*(1−Hct)); e) determining V_(PP), such thatV_(PP)=V_(RP)+V_(AC); f) withdrawing whole blood from the donor; g)introducing anticoagulant into the withdrawn whole blood at a specifiedratio (ACR); h) separating the withdrawn whole blood into a plasmaproduct and a second component comprising red blood cells; i) collectingthe plasma product in a plasma collection container; j) after a desiredamount of whole blood has been withdrawn from the donor, returning thered blood cells to the donor; and k) determining the Hct of the donorand V_(PP) prior to each collection phase.

In a sixth aspect, steps d)-k) are continued until a measured volume ofplasma product in the collection container equals V_(PP).

In a seventh aspect, V_(RP) is determined by establishing the V_(RP) foreach of a plurality of ranges of donor weight, and selecting the V_(RP)for the range of weight that is inclusive of the weight of the donor.The ranges of donor weight may be in three categories from 110 to 149lbs., 150 to 174 lbs., and 175 lbs. and up.

In an eighth aspect, V_(RP)=K₁*W_(kg).

In a ninth aspect, V_(RP) is no greater than 28.6% of (1−Hct)*(V_(b)).

In a tenth aspect, V_(b) is determined using one of Nadler's equations,Gilcher's Rule of Five, the standards of the ICSH, and any othergenerally accepted methodology.

In an eleventh aspect, V_(RP)=W_(kg)*10 mL/kg.

In a twelfth aspect, when donor parameters are used to estimate a totalblood volume (V_(b)) for the donor, V_(RP)=K₂*V_(b).

In a thirteenth aspect, an automated system for separating plasma fromwhole blood is provided comprising a reusable hardware component and adisposable kit. The disposable kit further comprises i) a separator forseparating whole blood into a plasma fraction and a concentrated cellfraction, the separator having an input having a blood line integrallyconnected thereto for transporting whole blood from a donor to theseparator, a plasma output port integrally connected to a plasmacollection container by a plasma line, and a concentrated cell outletport integrally connected to a reservoir for receipt of concentratedcells prior to reinfusion to the donor; ii) a donor line terminating ina venipuncture needle for transporting whole blood from a donor to theblood line, iii) an anticoagulant line integrally connected to the bloodline and configured to be connected to a source of anticoagulant fortransporting anticoagulant to the donor line, iv) a saline lineconfigured to be attached to a source of saline for transporting salineto the blood line, and v) a reinfusion line for transportingconcentrated cells from the reservoir to the donor line. The reusablehardware component further comprises i) a first peristaltic pump fordelivering anticoagulant at a controlled rate into the blood line duringa collection phase, ii) a second pump for delivering anticoagulatedwhole blood to the separator during the collection phase and forreturning concentrated cellular components during a reinfusion phase,iii) a third pump for delivering concentrated cellular components fromthe separator to the reservoir during the collection phase, iv) a clampassociated with each of the blood line, plasma line, reinfusion line andsaline line, v) a weigh scale for weighing each of the plasma collectioncontainer, the reservoir and the source of anticoagulant, and vi) aprogrammable controller comprising a touch screen for receiving inputfrom an operator, the programmable controller configured to receive asignal from each of the weigh scales and to automatically operate thefirst, second and third pumps and the clamps to separate whole bloodinto a plasma fraction and a concentrated cell fraction during thecollection phase and to return concentrated cells to the donor duringthe reinfusion stage. The programmable controller is further configuredto determine the weight of the plasma fraction to be collected in theplasma collection container in accordance with any of the aspectsdescribed herein, and to terminate the collection phase upon receiving asignal from the weigh scale for the plasma collection container equal tothe weight of the plasma fraction determined by the controller. Indetermining the target amount for the plasma product to be collected,the controller may be configured to calculate the hematocrit of thedonor prior to the collection phase of each cycle. Alternatively, oradditionally, the controller may receive a signal from a sensor or thelike that is indicative of the donor's hematocrit. Further, the amountof plasma product in the plasma collection container may be determinedby, e.g., the weigh scale associated with the plasma collection. In oneembodiment, the separator comprises a spinning membrane separator.

It will be understood that the embodiments described are illustrative ofsome of the applications of the principles of the present subjectmatter. Numerous modifications may be made by those skilled in the artwithout departing from the spirit and scope of the claimed subjectmatter, including those combinations of features that are individuallydisclosed or claimed herein. For these reasons, the scope of the claimsis not limited to the above-description, but is set forth in thefollowing claims.

1.-41. (canceled)
 42. A system for collecting plasma comprising: avenipuncture needle for drawing whole blood from a donor; a bloodseparator for separating the whole blood into a plasma product and asecond blood component comprising red blood cells, the blood separatorhaving a plasma output port connected to a plasma line for sending theplasma product component to a plasma product collection container; adonor line fluidly connected to the venipuncture needle for introducingthe whole blood from the donor to the separator and for returningconcentrated red blood cells to the donor; an anticoagulant lineconnected to an anticoagulant source, the anticoagulant line configuredto combine anticoagulant with the whole blood from the donor; and acontroller programmed to control the operation of the blood componentseparation device, the controller programmed to (1) calculate a targetdonor raw plasma volume (V_(RP)) that may be collected prior to aninitial draw phase and/or a target plasma product volume (V_(PP)) to becollected based, at least in part, on a weight, height and sex of thedonor and a hematocrit of the donor and the volume of anticoagulant tobe added to the target donor raw plasma volume based on an anticoagulantratio (ACR) and the hematocrit (HCT) of the donor such thatV_(PP)/V_(RP)=(ACR*(1−Hct/100)+1)/(ACR*(1−HCT/100)).
 43. The system ofclaim 42 wherein the controller is further configured to determine thehematocrit of the donor and the target plasma product collection volumeprior to any draw phase subsequent to the initial draw phase.
 44. Thesystem of claim 42 wherein the controller is further configured toinitiate a final return of the second blood component when a measuredvolume of plasma product in the plasma collection container equals thetarget plasma product collection volume.
 45. The system of claim 43wherein the controller is further configured to initiate a final returnof the second blood component when a measured volume of plasma productin the plasma collection container equals the target plasma productcollection volume.
 46. The system of claim 42 wherein the controller isfurther programmed to account for anticoagulant introduced into theplasma collection container separately from the plasma product.
 47. Thesystem of claim 42 wherein the controller is further configured toaccount for anticoagulant introduced into the plasma collectioncontainer separate from the plasma product attributable to a priming orother pre-processing step.
 48. The system of claim 42 wherein thecontroller is further programmed to determine the target plasma productcollection volume based on a starting/initial hematocrit for the donorand a changed hematocrit of the donor.
 49. The system of claim 42wherein the controller is further programmed to perform qualificationscreening of the donor based on donor parameters.
 50. The system ofclaim 43 wherein the controller is further configured to determine avolume of interstitial fluid that has shifted based on the volume ofplasma collected and to include the shifted volume of interstitial fluidwhen determining the donor's hematocrit.
 51. A method for collectingplasma comprising: a) determining a weight, height and sex of a donor;b) determining a hematocrit of the donor; c) prior to initiating a drawphase, determining a volume of raw plasma and/or a target plasma productcollection volume to be collected based at least in part on the weight,height, sex and hematocrit of the donor; d) withdrawing whole blood fromthe donor; e) adding anticoagulant to the whole blood at a specifiedratio; f) separating anticoagulated whole blood into anticoagulatedplasma and a second anticoagulated component comprising red blood cells;g) collecting the separated anticoagulated plasma in a container; and h)after the previously determined volume of raw plasma and/or targetvolume of plasma product has been collected, initiating a return of thesecond anticoagulated component to the donor.
 52. The method of claim 51further comprising accounting for anticoagulant in the containerintroduced into the container separately from the anticoagulated plasma.53. The method of claim 51 further comprising accounting foranticoagulant in the container introduced into the container separatelyfrom the anticoagulated plasma.
 54. The method of claim 52 wherein theanticoagulant in the container introduced separately from theanticoagulated plasma is attributable to anticoagulant used for apriming or other pre-processing step.
 55. The method of claim 51 furthercomprising determining the target plasma product collection volume basedon a starting/initial hematocrit for the donor and a changed hematocritof the donor.
 56. The method of claim 51 further comprising performingqualification screening of the donor based on donor parameters.
 57. Themethod of claim 51 further comprising determining a volume ofinterstitial fluid that has shifted based on the volume of plasmacollected and to include the shifted volume of interstitial fluid whendetermining the donor's hematocrit.